Measuring the levels of small molecules in the blood may be able to identify individuals at elevated risk of developing type 2 diabetes as much as a decade before symptoms of the disorder appear.
In a report receiving advance online release in Nature Medicine, a team led by Massachusetts General Hospital (MGH) researchers describes finding that levels of five amino acids not only indicated increased diabetes risk in a general population but also could differentiate, among individuals with traditional risk factors such as obesity, those most likely to actually develop diabetes.
New technologies to measure levels of metabolites — small molecules produced by metabolic activities and released into the bloodstream — are giving investigators increased insight into an individual’s metabolic status. Since the diagnosis of type 2 diabetes marks the culmination of a years-long breakdown of the body’s system for metabolizing glucose, the ability to detect that breakdown at a stage when lifestyle changes could halt the process may significantly reduce the incidence of the disease. Known risk factors such as obesity and elevated glucose levels often signify that diabetes actually is present, so earlier identification of at-risk individuals is critical to more effective preventive measures, the authors note.
Some earlier studies had found elevated levels of certain amino acids in individuals who are obese or have insulin resistance, a condition that precedes full-blown type 2 diabetes. But no previous study examined whether levels of these or other metabolites predicted the future development of diabetes in currently healthy individuals. The current study began with an analysis of data from the Framingham Offspring Study, which follows a group of adult children of participants in the original Framingham Heart Study. Out of 2,400 study participants who entered the study in 1991 and 1995, about 200 developed type 2 diabetes during the following 12 years. Using the baseline blood samples, the research team measured levels of 61 metabolites in 189 participants who later developed diabetes and 189 others — matched for age, sex and diabetes risk factors such as obesity and fasting glucose levels — who remained diabetes free.
This analysis found that elevations in five amino acids — isoleucine, leucine, valine, tyrosine and phenylalanine — were significantly associated with the later development of type 2 diabetes. Several of these amino acids were the same ones found in smaller studies to be elevated in individuals with obesity or insulin resistance, and other evidence has suggested they may directly affect glucose regulation. The association of levels of these five amino acids with future diabetes development was replicated in 326 participants in the Malmo Diet and Cancer Study.
The investigators then found that measuring combinations of several metabolites, as opposed to a single amino acid, improved risk prediction. Overall, in individuals closely matched for traditional risk factors for type 2 diabetes, those with the highest levels of the three most predictive amino acids had a four to five times greater risk of developing diabetes than did those with the lowest levels.
Source: Massachusetts General Hospital, USA